Fig.5.

Intraperitoneal administration of SGC-PIKFYVE-1 reduces spared nerve injury (SNI)-induced nociceptive behaviors in male mice. (A) SNI model schematic and timeline of the experimental approach used to determine the antinociceptive effects of SGC-PIKFYVE-1 on tactile and cold allodynia in male mice. (B) Baseline paw withdrawal threshold measurements were conducted before intraperitoneal administration of SGC-PIKFYVE-1 in male mice with neuropathic pain. The time course of a single intraperitoneal (IP) injection of SGC-PIKFYVE-1 (3–30 mg/kg) or vehicle (DMSO 30 %) on mechanical allodynia were measured from 0 to 6 h post injection on day 28 post-SNI (n = 8 mice). Von Frey filaments were used to determine the 50 % paw withdrawal threshold using the up-down method. Results were compared using two-way ANOVA with factors: time * treatment, followed by the Tukey post hoc test. **P < 0.01 and ***P < 0.001 vs vehicle group. (C) Quantification of area under the curve (AUC) of the time course of the effect induced by SGC-PIKFYVE-1 from 0 to 6 h (n = 8 mice). Results were analyzed using one-way ANOVA, followed by the Dunnett post hoc test. ***P < 0.001 vs vehicle group. (D) Baseline aversion time responses were performed before SGC-PIKFYVE-1 in male neuropathic mice. The time course of a single intraperitoneal (IP) injection of SGC-PIKFYVE-1 (30 mg/kg) or vehicle (DMSO 30 %) on cold allodynia were measured from 0 to 6 h post injection on day 28 post-SNI (n = 8 mice). Results were compared using two-way ANOVA, with factors: time * treatment, followed by the Tukey post hoc test. (E) Quantification of AUC in panel D between 0 and 6 h. SGC-PIKFYVE-1 (30 mg/kg) reversed SNI-induced cold allodynia. ***P < 0.001 vs vehicle group; one-way ANOVA followed by the Dunnett post hoc test. n = 8 mice. For all panels, error bars indicate mean ± SEM. B, Baseline.